Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke.

Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13-48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = -8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke. Clinical Trial Registration: www.ClinicalTrials.gov, identifier (NCT03592745).

Robotic Kinematic measures of the arm in chronic Stroke: part 1 - Motor Recovery patterns from tDCS preceding intensive training.

BACKGROUND: Effectiveness of robotic therapy and transcranial direct current stimulation is conventionally assessed with clinical measures. Robotic metrics may be more objective and sensitive for measuring the efficacy of interventions on stroke survivor's motor recovery. This study investigated if robotic metrics detect a difference in outcomes, not seen in clinical measures, in a study of transcranial direct current stimulation (tDCS) preceding robotic therapy. Impact of impairment severity on intervention response was also analyzed to explore optimization of outcomes by targeting patient sub-groups. METHODS: This 2020 study analyzed data from a double-blind, sham-controlled, randomized multi-center trial conducted from 2012 to 2016, including a six-month follow-up. 82 volunteers with single chronic ischemic stroke and right hemiparesis received anodal tDCS or sham stimulation, prior to robotic therapy. Robotic therapy involved 1024 repetitions, alternating shoulder-elbow and wrist robots, for a total of 36 sessions. Shoulder-elbow and wrist kinematic and kinetic metrics were collected at admission, discharge, and follow-up. RESULTS: No difference was detected between the tDCS or sham stimulation groups in the analysis of robotic shoulder-elbow or wrist metrics. Significant improvements in all metrics were found for the combined group analysis. Novel wrist data showed smoothness significantly improved (P < ·001) while submovement number trended down, overlap increased, and interpeak interval decreased. Post-hoc analysis showed only patients with severe impairment demonstrated a significant difference in kinematics, greater for patients receiving sham stimulation. CONCLUSIONS: Robotic data confirmed results of clinical measures, showing intensive robotic therapy is beneficial, but no additional gain from tDCS. Patients with severe impairment did not benefit from the combined intervention. Wrist submovement characteristics showed a delayed pattern of motor recovery compared to the shoulder-elbow, relevant to intensive intervention-related recovery of upper extremity function in chronic stroke. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663 .

Robotic Kinematic measures of the arm in chronic Stroke: part 2 - strong correlation with clinical outcome measures.

BACKGROUND: A detailed sensorimotor evaluation is essential in planning effective, individualized therapy post-stroke. Robotic kinematic assay may offer better accuracy and resolution to understand stroke recovery. Here we investigate the added value of distal wrist measurement to a proximal robotic kinematic assay to improve its correlation with clinical upper extremity measures in chronic stroke. Secondly, we compare linear and nonlinear regression models. METHODS: Data was sourced from a multicenter randomized controlled trial conducted from 2012 to 2016, investigating the combined effect of robotic therapy and transcranial direct current stimulation (tDCS). 24 kinematic metrics were derived from 4 shoulder-elbow tasks and 35 metrics from 3 wrist and forearm evaluation tasks. A correlation-based feature selection was performed, keeping only features substantially correlated with the target attribute (R > 0.5.) Nonlinear models took the form of a multilayer perceptron neural network: one hidden layer and one linear output. RESULTS: Shoulder-elbow metrics showed a significant correlation with the Fugl Meyer Assessment (upper extremity, FMA-UE), with a R = 0.82 (P < 0.001) for the linear model and R = 0.88 (P < 0.001) for the nonlinear model. Similarly, a high correlation was found for wrist kinematics and the FMA-UE (R = 0.91 (P < 0.001) and R = 0.92 (P < 0.001) for the linear and nonlinear model respectively). The combined analysis produced a correlation of R = 0.91 (P < 0.001) for the linear model and R = 0.91 (P < 0.001) for the nonlinear model. CONCLUSIONS: Distal wrist kinematics were highly correlated to clinical outcomes, warranting future investigation to explore our nonlinear wrist model with acute or subacute stroke populations. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663 .

Non-invasive treatment of patients with upper extremity spasticity following stroke using paired trans-spinal and peripheral direct current stimulation.

BACKGROUND: Muscle spasticity is a common impediment to motor recovery in patients with chronic stroke. Standard-of-care treatments such as botulinum toxin injections can temporarily relieve muscle stiffness and pain associated with spasticity, but often at the expense of increased muscle weakness. Recent preclinical investigations of a non-invasive treatment that pairs trans-spinal direct current stimulation and peripheral nerve direct current stimulation (tsDCS+pDCS) provided promising data for a novel approach based on bioelectronic medicine for the treatment of patients with post-stroke spasticity. METHODS: Twenty-six patients with upper limb hemiparesis and wrist spasticity at least 6 months after their initial stroke participated in this single-blind crossover design study to test whether tsDCS+pDCS reduces chronic upper-extremity spasticity. Subjects received five consecutive daily sessions (20 min of stimulation or sham) of anodal tsDCS+pDCS, separated by a one-week washout period. The sham condition always preceded the active condition. Clinical and objective measures of spasticity and motor function were collected before and after each condition, and for five weeks after the completion of the active intervention. RESULTS: Subjects treated with active tsDCS+pDCS demonstrated significant reductions in both Modified Tardieu Scale scores (summed across the upper limb, P < 0.05), and in objective torque measures (Nm) of the spastic catch response at the wrist flexor (P < 0.05), compared to the sham condition. Motor function also improved significantly (measured by the Fugl-Meyer and Wolf Motor Function Test; P < 0.05 for both tests) after active treatment. CONCLUSIONS: tsDCS+pDCS intervention alone significantly reduced upper limb spasticity in participants with stroke. Decreased spasticity was persistent for five weeks after treatment, and was accompanied by improved motor function even though patients were unsupervised and there was no prescribed activity or training during that interval. TRIAL REGISTRATION: NCT03080454, March 15, 2017.

Intensive seated robotic training of the ankle in patients with chronic stroke differentially improves gait.

BACKGROUND: Robotic driven treatment plans targeting isolated joints of the upper limb have improved the sensorimotor condition of patients with stroke. Similar intensive efforts to allay lower limb gait impairment have not been so successful. In patients with stroke, targeted robot assisted training of the ankle joint, in a seated position, has demonstrated significant alterations in ankle stiffness and foot-ankle orientation at foot strike which may provide a new treatment option for gait impairment. OBJECTIVE: To determine if isolated robot-assisted training of the ankle joint improves chronic hemiparetic gait in patients with stroke who are categorized according to baseline gait impairment. METHODS: Patients with chronic stroke (>6mo) and hemiparetic gait (N = 29) received 18 sessions of isolated robot-assisted motor training of the ankle (3×/week for 6 weeks). All participants had stable clinical baseline scores across three admission measures, and no participant was receiving simultaneous outpatient rehabilitation. Baseline gait speed determined three impairment groups: high, >0.8 m/s; medium, 0.4-0.8 m/s; low, <0.4 m/s. Outcome measures included the Berg Balance Scale, the 6 Minute Walk Test, and the 10 Meter Walk Test, and were recorded upon admission, discharge, and 3 months following intervention. RESULTS: Three distinct and significant between-group patterns of recovery emerged for gait speed. The within-group analysis showed that the medium and high group exhibited significant improvements in gait speed and endurance upon discharge, that were maintained at 3-months. Gait speed improvements were clinically significant (>0.16 m/s) for the high function group across all gait speed and endurance measures at discharge and at 3 months. The moderate group also exhibited clinically significant improvements at follow-up on the 10 Meter Walk Test, fast pace (0.16 m/sec), and approached clinical significance for the 10 Meter Walk comfortable pace (0.12 m/sec). The low group had small but significant improvements, at discharge on two of the three gait measures, and these improvements were maintained at 3 months. For balance measures, the low and moderate impairment groups had significant improvements at discharge that were robust on follow-up measure. The high function group demonstrated no significant change in balance. CONCLUSIONS: Joint-specific robotic training of the paretic ankle provided the most benefit to individuals with moderate or mild gait speed impairments after stroke. Baseline gait speed function (low, moderate, high) was associated with three distinct recovery profiles. This suggests that severity-specific intervention may be critical to improving efficiency of stroke recovery.